Targeted Screening of Curcumin Derivatives as Pancreatic Lipase Inhibitors Using Computer-Aided Drug Design.

Curcumin has demonstrated promising preclinical antiobesity effects, but its low bioavailability makes it difficult to exert its full effect at a suitable dose. The objective of this study was to screen curcumin derivatives with enhanced bioavailability and lipid-lowering activity under the guidance of computer-aided drug design (CADD). CAAD was used to perform virtual assays on curcumin derivatives to assess their pharmacokinetic properties and effects on pancreatic lipase activity. Subsequently, 19 curcumin derivatives containing 5 skeletons were synthesized to confirm the above virtual assay. The in vitro pancreatic lipase inhibition assay was employed to determine the half-maximal inhibitory concentration (IC50) of these 19 curcumin derivatives. Based on CADD analysis and in vitro pancreatic lipase inhibition, 2 curcumin derivatives outperformed curcumin in both aspects. Microscale thermophoresis (MST) experiments were employed to assess the binding equilibrium constants (K d) of the aforementioned 2 curcumin derivatives, curcumin, and the positive control drug with pancreatic lipase. Through virtual screening utilizing a chemoinformatics database and molecular docking, 6 derivatives of curcumin demonstrated superior solubility, absorption, and pancreatic lipase inhibitory activity compared to curcumin. The IC50 value for 1,7-bis(4-hydroxyphenyl)heptane-3,5-dione (C4), which displayed the most effective inhibitory effect, was 42.83 µM, while the IC50 value for 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (C6) was 98.62 µM. On the other hand, the IC50 value for curcumin was 142.24 µM. The MST experiment results indicated that the K d values of C4, C6, and curcumin were 2.91, 18.20, and 23.53 µM, respectively. The results of the activity assays exhibited a relatively high degree of concordance with the outcomes yielded by CADD screening. Under the guidance of CADD, the targeted screening of curcumin derivatives with excellent properties in this study exhibited high-efficiency and low-cost benefits.

ZFYVE19 deficiency: a ciliopathy involving failure of cell division, with cell death.

BACKGROUND AND AIMS: Variants in ZFYVE19 underlie a disorder characterised by progressive portal fibrosis, portal hypertension and eventual liver decompensation. We aim to create an animal model to elucidate the pathogenic mechanism. METHODS: Zfyve19 knockout (Zfyve19-/- ) mice were generated and exposed to different liver toxins. Their livers were characterised at the tissue, cellular and molecular levels. Findings were compared with those in wild-type mice and in ZFYVE19-deficient patients. ZFYVE19 knockout and knockdown retinal pigment epithelial-1 cells and mouse embryonic fibroblasts were generated to study cell division and cell death. RESULTS: The Zfyve19-/- mice were normal overall, particularly with respect to hepatobiliary features. However, when challenged with α-naphthyl isothiocyanate, Zfyve19-/- mice developed changes resembling those in ZFYVE19-deficient patients, including elevated serum liver injury markers, increased numbers of bile duct profiles with abnormal cholangiocyte polarity and biliary fibrosis. Failure of cell division, centriole and cilia abnormalities, and increased cell death were observed in knockdown/knockout cells. Increased cell death and altered mRNA expression of cell death-related signalling pathways was demonstrated in livers from Zfyve19-/- mice and patients. Transforming growth factor-ß (TGF-ß) and Janus kinase-Signal Transducer and Activator of Transcription 3 (JAK-STAT3) signalling pathways were upregulated in vivo, as were chemokines such as C-X-C motif ligands 1, 10 and 12. CONCLUSIONS: Our findings demonstrated that ZFYVE19 deficiency is a ciliopathy with novel histological features. Failure of cell division with ciliary abnormalities and cell death activates macrophages and may thus lead to biliary fibrosis via TGF-ß pathway in the disease.

How does climate change affect potential yields of four staple grain crops worldwide by 2030?

Global food security basically depends on potential yields of staple grain crops worldwide, especially under climate change. However, most scholars use various models of production function in which climatic factors are often considered to estimate crop yield mostly at local or regional level. Therefore, in this paper: Potential yields of rice, wheat, maize and soybean worldwide by 2030 are projected creatively using Auto-regressive Integrated Moving Average and Trend Regressed (ARIMA-TR) model in which actual yields in recent two years are used for testing the reliability of projection and Gray System (GS) model for validating the test; Especially individual impacts of climate change on the productions of rice, wheat, maize and soybean worldwide since 1961 are analyzed by using unary regression model in which global mean temperature and land precipitation are independent variable while the yield of crop being dependent one, respectively. Results show that: by 2030, the ratio between average and top yields of world rice is projected to be 50.6% increasing, while those of world wheat, world maize and world soybean are projected to be 38.0% increasing, 14.7% decreasing and 72.5% increasing, respectively. Since 1961 global warming has exerted a negative impact on average yield of world rice less than on its top, a positive effect on average yield of world wheat while a negative impact on its top, a positive effect on average yield of world maize less than on its top, and a positive influence on average yield of world soybean while a negative one on its top, which might be slightly mitigated by 'Carbon Peak' target. The fluctuation of global rainfall contributes to the productions of these crops much less than global warming during same period. Our findings indicate that: to improve global production of four staple grain crops by 2030, the priorities of input should be given to either rice or wheat in both high and low yield countries, whereas to maize in high yield countries and to soybean in low yield countries. These insights highlight some difference from previous studies, and provide academia with innovative comprehension and policy-decision makers with supportive information on sustainable production of these four staple grain crops for global food security under climate change in the future.

Analysis of Key Genes and miRNA-mRNA Networks Associated with Glucocorticoids Treatment in Chronic Obstructive Pulmonary Disease.

Background: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear. Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained. Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated. Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated. Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.

The innovative checkpoint inhibitors of lung adenocarcinoma, cg09897064 methylation and ZBP1 expression reduction, have implications for macrophage polarization and tumor growth in lung cancer.

Lung cancer, a prevalent and aggressive disease, is characterized by recurrence and drug resistance. It is essential to comprehend the fundamental processes and discover novel therapeutic objectives for augmenting treatment results. Based on our research findings, we have identified a correlation between methylation of cg09897064 and decreased expression of ZBP1, indicating a link to unfavorable prognosis in patients with lung cancer. Furthermore, these factors play a role in macrophage polarization, with ZBP1 upregulated in M1 macrophages compared to both M0 and M2 polarized macrophages. We observed cg09897064 methylation in M2 polarization, but not in M0 and M1 polarized macrophages. ATACseq analysis revealed closed chromatin accessibility of ZBP1 in M0 polarized macrophages, while open accessibility was observed in both M1 and M2 polarized macrophages. Our findings suggest that ZBP1 is downregulated in M0 polarized macrophages due to closed chromatin accessibility and downregulated in M2 polarized macrophages due to cg09897064 methylation. Further investigations manipulating cg09897064 methylation and ZBP1 expression through overexpression plasmids and shRNAs provided evidence for their role in modulating macrophage polarization and tumor growth. ZBP1 inhibits M2 polarization and suppresses tumor growth, while cg09897064 methylation promotes M2 polarization and macrophage-induced tumor growth. In mechanism investigations, we found that cg09897064 methylation impairs CEBPA binding to the ZBP1 promoter, leading to decreased ZBP1 expression. Clinical experiments were conducted to validate the correlation between methylation at cg09897064, ZBP1 expression, and macrophage M2 polarization. Targeting these factors may hold promise as a strategy for developing innovative checkpoint inhibitors in lung cancer treatment.

Pyrenecarboxaldehyde@Graphene Oxide Acted as a Highly Efficient ECL Emitter and Target-Triggered the Recyclable Cascade System as an Amplifier for Ultrasensitive APE1 Activity Detection.

Herein, pyrenecarboxaldehyde@graphene oxide (Pyc@GO) sheets with highly efficient electrochemiluminescence (ECL) as emitters were prepared by a noncovalent combination to develop a neoteric ECL biosensing platform for the ultrasensitive assessment of human apurinic/apyrimidinic endonuclease1 (APE1) activity. Impressively, the pyrenecarboxaldehyde (Pyc) molecules were able to form stable polar functional groups on the surface of GO sheets through the noncovalent π-π stacking mechanism to prevent intermolecular restacking and simultaneously generate Pyc@GO sheets. Compared with the tightly packed PAH nanocrystals, the Pyc@GO sheets significantly reduced internal filtering effects and diminished nonactivated emitters to enhance ECL intensity and achieve strong ECL emission. Furthermore, the APE1-activated initiators could trigger the recyclable cascade amplified system based on the synergistic cross-activation between catalytic hairpin assembly (CHA) and DNAzyme, which improved the signal amplification and transduction ability. Consequently, the developed ECL platform for the detection of APE1 activity displayed exceptional sensitivity with a low detection limit of 4.6 × 10-9 U·mL-1 ranging from 10-8 to 10-2 U·mL-1. Therefore, the proposed strategy holds great promise for the future development of sensitive and reliable biosensing platforms for the detection of various biomarkers.

Contribution of rumination and psychological resilience to post-traumatic growth of front-line healthcare workers in mobile cabin hospitals under Normalized epidemic Prevention and Control Requirements.

To understand the level of post-traumatic growth (PTG) and influencing factors among front-line healthcare workers (HCWs) working in mobile cabin hospitals treating patients with Coronavirus Disease 2019 (COVID-19) under the Normalized Epidemic Prevention and Control Requirements adopted in China. A random sampling method was used to select 540 HCWs of the Chongqing-aid-Shanghai medical team from April to May 2022 as the study participants. Participants completed a general information questionnaire, the Post-traumatic Growth Inventory-Chinese version (PTGI-C), the Chinese version of the Connor-Davidson Resilience Scale (CD-RISC) and the Chinese Event Related Rumination Inventory (C-ERRI). Among the 540 included HCWs, 83.15 % were nurses and 78.89 % were women. The average scores for PTG (62.25 ± 16.73) and psychological resilience (64.22 ± 15.38) were at moderate levels, and the average score for rumination was low (21.62 ± 10.77). Pearson correlation analysis showed that CD-RISC and C-ERRI scores were positive with the PTGI-C score (r = 0.528, 0.316, P < 0.001). Multiple linear regression analysis identified psychological training or intervention during the COVID-19 epidemic (ß = 2.353, P = 0.044), psychological resilience (ß = 0.525, P < 0.001) and deliberate rumination (ß = 0.732, P < 0.001) as factors significantly associated with the PTG of front-line HCWs, which together explained 36.8 % of the total variance in PTG (F[5,539] = 63.866, P < 0.001). In general, psychological resilience and deliberate rumination can promote PTG among HCWs and can be improved by strengthening psychological training and interventions for HCWs working under the Normalized Epidemic Prevention and Control Requirements.

Comparative analysis of the synergetic effects of Diwuyanggan prescription on high fat diet-induced non-alcoholic fatty liver disease using untargeted metabolomics.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide and had no approved pharmacological treatments. Diwuyanggan prescription (DWYG) is a traditional Chinese medicine preparation composed of 5 kinds of herbs, which has been used for treating chronic liver diseases in clinic. Whereas, the synergistic mechanism of this prescription for anti-NAFLD remains unclear. In this study, we aimed to demonstrate the synergetic effect of DWYG by using the disassembled prescriptions and untargeted metabolomics research strategies. The therapeutic effects of the whole prescription of DWYG and the individual herb were divided into six groups according to the strategy of disassembled prescriptions, including DWYG, Artemisia capillaris Thunb. (AC), Curcuma longa L. (CL), Schisandra chinensis Baill. (SC), Rehmannia glutinosa Libosch. (RG) and Glycyrrhiza uralensis Fisch. (GU) groups. The high fat diets-induced NAFLD mice model was constructed to evaluate the efficacy effects of DWYG. An untargeted metabolomics based on the UPLC-QTOF-MS/MS approach was carried out to make clear the synergetic effect on the regulation of metabolites dissecting the united mechanisms. Experimental results on animals revealed that the anti-NAFLD effect of DWYG prescription was better than the individual herb group in reducing liver lipid deposition and restoring the abnormality of lipidemia. In addition, further metabolomics analysis indicated that 23 differential metabolites associated with the progression of NAFLD were identified and 19 of them could be improved by DWYG. Compared with five single herbs, DWYG showed the most extensive regulatory effects on metabolites and their related pathways, which were related to lipid and amino acid metabolisms. Besides, each individual herb in DWYG was found to show different degrees of regulatory effects on NAFLD and metabolic pathways. SC and CL possessed the highest relationship in the regulation of NAFLD. Altogether, these results provided an insight into the synergetic mechanisms of DWYG from the metabolic perspective, and also supported a scientific basis for the rationality of clinical use of this prescription.

Analysis of influencing factors of job demands of healthcare workers working in mobile cabin hospitals in China.

AIM: To explore the job demands of healthcare workers (HCWs) working in mobile cabin hospitals in Shanghai and identify the influencing factors. DESIGN: The study had a cross-sectional design. METHODS: Using the convenience sampling method, we selected 1223 HCWs (medical team members) working in these mobile cabin hospitals during April-May 2022. The findings of the general information questionnaire and the hierarchy scale of job demands of HCWs working in mobile cabin hospitals were used for the investigation. RESULTS: The total score of job demands of the included HCWs was 132.26 ± 9.53; the average score of the items was 4.73 ± 0.34. Multivariate linear regression analyses showed that the following HCWs had significantly higher job demands: female HCWs and HCWs who received psychological training or intervention during the COVID-19 pandemic, were satisfied with the doctor/nurse-patient relationship, received support from family members/friends/colleagues, believed that the risk of working in mobile cabin hospitals was high, had adapted to the working environment of mobile cabin hospitals and had college/undergraduate level of education. They would benefit from increased social support and better training in terms of psychological coping mechanisms(both theoretical knowledge and applicable skills) and COVID-19 prevention,control and treatment abilities.

Latent class analysis of healthcare workers' perceptions of workers' job demands in mobile cabin hospitals in China.

BACKGROUND: Owing to the outbreak of the Omicron variant of SARS-CoV-2 in Shanghai, China, partitioned dynamic closure and control management plans were implemented on March 28, 2022. This created huge emergency pressure on Shanghai's medical and healthcare systems. However, the perceptions of job demands of healthcare workers (HCWs) and classification of frontline HCWs in mobile cabin hospitals are unknown. METHODS: In this study, we investigated the job demands of 1223 frontline HCWs working in mobile cabin hospitals during the COVID-19 pandemic April 2022 to May 2022. We performed latent class analysis to identify classification features of job demands. A binary multivariate logistic regression model was used to explore the influencing factors of latent class. RESULTS: The total mean job demand score was 132.26 (SD = 9.53), indicating a high level of job demand. A two-class model provided the best fit. The two classes were titled "middle-demand group" (17.66%) and "high-demand group" (82.34%). A regression analysis suggested that female HCWs, HCWs satisfied with the doctor/nurse-patient relationship, HCWs who believed that the risk of working in mobile cabin hospitals was high, and HCWs without physical discomfort during the pandemic were more likely to be in the "high-demand group". CONCLUSION: Characteristics of the "high-demand group" subtype suggest that attention should be paid to the physical condition of frontline HCWs and the job demands of female HCWs. Managers should strengthen the training of HCWs in terms of their communication skills as well as their knowledge and technical skills to aid epidemic prevention and control.

Temporally gene knockout using heat shock-inducible genome-editing system in plants.

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) has emerged as a powerful tool to generate targeted loss-of-function mutations for functional genomic studies. As a next step, tools to generate genome modifications in a spatially and temporally precise manner will enable researchers to further dissect gene function. Here, we present two heat shock-inducible genome-editing (IGE) systems that efficiently edit target genes when the system is induced, thus allowing us to target specific developmental stages. For this conditional editing system, we chose the natural heat-inducible promoter from heat-shock protein 18.2 (HSP18.2) from Arabidopsis thaliana and the synthetic heat-inducible promoter heat shock-response element HSE-COR15A to drive the expression of Cas9. We tested these two IGE systems in Arabidopsis using cyclic or continuous heat-shock treatments at the seedling and bolting stages. A real-time quantitative polymerase chain reaction analysis revealed that the HSP18.2 IGE system exhibited higher Cas9 expression levels than the HSE-COR15A IGE system upon both cyclic and continuous treatments. By targeting brassinosteroid-insensitive 1 (BRI1) and phytoene desaturase (PDS), we demonstrate that both cyclic and continuous heat inductions successfully activated the HSP18.2 IGE system at the two developmental stages, resulting in highly efficient targeted mutagenesis and clear phenotypic outcomes. By contrast, the HSE-COR15A IGE system was only induced at the seedling stage and was less effective than the HSP18.2 IGE system in terms of mutagenesis frequencies. The presented heat shock-IGE systems can be conditionally induced to efficiently inactivate genes at any developmental stage and are uniquely suited for the dissection and systematic characterization of essential genes.

An IncN-ST7 epidemic plasmid mediates the dissemination of carbapenem-resistant Klebsiella pneumoniae in a neonatal intensive care unit in China over 10 years.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has widely disseminated globally, but its epidemiological characterization and clinical significance in paediatric patients are not well understood. In this study, we aimed to trace the dissemination dynamics of CRKP in the neonatal intensive care unit (NICU) of a tertiary hospital over a 10-y period. METHODS: We collected 67 non-duplicate K. pneumoniae species complex isolates from the NICU with patient metadata during 2009-2018. Antimicrobial susceptibility was determined by the agar or broth microdilution method. Risk factors for CRKP-positive patients were identified by univariate and multivariate analysis. Genetic characterization was dissected by whole-genome sequencing. Plasmid transmissibility, stability, and fitness were assessed. RESULTS: Thirty-four of 67 isolates (50.75%) were identified as CRKP. Premature rupture of membranes, gestational age, and invasive procedures are independent risk factors for CRKP-positive patients. The annual isolation rate of CRKP varied between 0% and 88.9%, and multiple clonal replacements were observed during the study period, which could be largely due to the division of the NICU. All but one CRKP produced IMP-4 carbapenemase, which was encoded by an IncN-ST7 epidemic plasmid, suggesting that the IncN-ST7 plasmid mediated the CRKP dissemination in the NICU over 10 y. The same plasmid was found in several CRKP isolates from adult patients, of which two ST17 isolates from the neurosurgery department shared a high homology with the ST17 isolates from the NICU, indicating possible cross-departmental transmission. CONCLUSION: Our study highlights the urgent need for infection control measures targeting high-risk plasmids like IncN-ST7.

Relationship between rumination and post-traumatic growth in mobile cabin hospital nurses: The mediating role of psychological resilience.

Psychological resilience helps individuals to actively respond to various emergencies, but its mediating role between the rumination and post-traumatic growth (PTG) of nurses remains unknown. Our study aimed to explore the extent to which psychological resilience mediates the association between rumination and PTG among nurses working in mobile cabin hospitals. This cross-sectional survey was conducted on 449 medical team members working in mobile cabin hospitals to support the prevention and control of coronavirus disease 2019 in Shanghai, China in 2022. Pearson correlation analysis was applied to assess the correlation between rumination, psychological resilience, and PTG. Structural equation models were used to examine the mediating role of psychological resilience between rumination and PTG. Our study results showed that deliberate rumination directly promoted psychological resilience and PTG and had positive effects on PTG through the mediating effect of psychological resilience. Invasive rumination had no direct effect on PTG. However, it had a negative effect on PTG through the mediating effect of psychological resilience. Together the results of this study indicate that the mediating effect of psychological resilience was significant in the association of rumination and PTG among mobile cabin hospital nurses, with a higher individual psychological resilience level helping nurses to achieve PTG. Therefore, targeted interventions should be implemented to improve nurses' psychological resilience and guide their rapid growth.

A point mutation in recC associated with subclonal replacement of carbapenem-resistant Klebsiella pneumoniae ST11 in China.

Adaptation to selective pressures is crucial for clinically important pathogens to establish epidemics, but the underlying evolutionary drivers remain poorly understood. The current epidemic of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to public health. In this study we analyzed the genome sequences of 794 CRKP bloodstream isolates collected in 40 hospitals in China between 2014 and 2019. We uncovered a subclonal replacement in the predominant clone ST11, where the previously prevalent subclone OL101:KL47 was replaced by O2v1:KL64 over time in a stepwise manner. O2v1:KL64 carried a higher load of mobile genetic elements, and a point mutation exclusively detected in the recC of O2v1:KL64 significantly promotes recombination proficiency. The epidemic success of O2v1:KL64 was further associated with a hypervirulent sublineage with enhanced resistance to phagocytosis, sulfamethoxazole-trimethoprim, and tetracycline. The phenotypic alterations were linked to the overrepresentation of hypervirulence determinants and antibiotic genes conferred by the acquisition of an rmpA-positive pLVPK-like virulence plasmid and an IncFII-type multidrug-resistant plasmid, respectively. The dissemination of the sublineage was further promoted by more frequent inter-hospital transmission. The results collectively demonstrate that the expansion of O2v1:KL64 is correlated to a repertoire of genomic alterations convergent in a subpopulation with evolutionary advantages.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

Cross-sectional survey of smartphone addiction and its relationship with personality traits among medical students.

OBJECTIVE: To understand the current smart phone addiction tendency (SPAT) in medical university students and relationship with personality traits. METHODS: A cross-sectional study from September 2019 to December 2019 selected medical students from Hubei University of China by cluster sampling. Questionnaires were administered to measure smart phone addiction tendency and personality traits. RESULTS: The prevalence of SPAT among 972 medical students was 24.3%. The prevalence was higher in students from one-child family than those with siblings (28.2% vs. 21.7%), and higher among students from urban families than those from rural ones (29.2% vs. 19.7%).Multivariate logistic regression analysis showed that extraversion and neuroticism were correlated with SPAT, with odds ratio and 95% confidence interval being equal to 1.070 (1.011-1.133) and 0.838 (0.795-0.844), respectively. CONCLUSIONS: The prevalence of SPAT was high in medical college students. Extraversion and neuroticism were risk and protective factors for SPAT. Long duration phone use and a low number of physical workouts predicted high SPAT.

Addition of the T5 exonuclease increases the prime editing efficiency in plants.

Prime editing (PE) is a versatile genome editing tool without the need for double-stranded DNA breaks or donor DNA templates, but is limited by low editing efficiency. We previously fused the M-MLV reverse transcriptase to the Cas9 nickase, generating the PE2 (v1) system, but the editing efficiency of this system is still low. Here we develop different versions of PE2 by adding the 5'-to-3' exonuclease at different positions of the nCas9-M-MLV RT fusion protein. PE2 (v2), in which the T5 exonuclease fused to the N-terminus of the nCas9-MMLV fusion protein enhances prime editing efficiency of base substitutions, deletions, and insertions at several genomic sites by 1.7- to 2.9-fold in plant cells compared to PE2 (v1). The improved editing efficiency of PE2 (v2) is further confirmed by generating increased heritable prime edits in stable transgenic plants compared to the previously established PE-P1, PE-P2, and PPE systems. Using PE2 (v2), we generate herbicide-resistant rice by simultaneously introducing mutations causing amino acid substitutions at two target sites. The PE efficiency is further improved by combining PE2 (v2) and dual-pegRNAs. Taken together, the increased genome editing efficiency of PE2 (v2) developed in this study may enhance the applications of PE in plants.

Autophagy, cell death, and cytokines in K. pneumoniae infection: therapeutic perspectives.

Klebsiella pneumoniae is a notorious nosocomial pathogen causing a wide range of infections. The increasing trend of antimicrobial resistance obtained by the species immensely highly challenges the clinical treatment, representing a large threat to the global health care network. In particular, the recent convergence of multidrug resistance and hypervirulence in K. pneumoniae further worsens clinical outcomes, resulting in high mortality. Developments of new therapeutics become urgent, and immunotherapy based on antagonizing the anti-immune strategies of pathogens is a promising strategy, which requires the understanding of immune evasion mechanism in the context of the host-pathogen interactions. However, the underlying mechanisms employed by K. pneumoniae to counteract host immune responses, especially autophagy and cell death, have not been systematically reviewed and discussed yet. This review aims to summarize the tremendous progress that has been made to illuminate the landscape of cell signalling triggered by K. pneumoniae infection, especially in aspects of manipulating autophagy, cell death, and cytokine production.

Clinical comprehensive evaluation of recombinant Mycobacterium tuberculosis fusion protein / 中国药房

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Promoting high-quality therapeutic research on nontuberculous mycobacteria pulmonary disease in China / 中华临床感染病杂志

The incidence of pulmonary disease caused by nontuberculous mycobacteria infection (NTM-PD) shows a growing trend. The treatment of NTM-PD is of low cure rate, high mortality and recurrence rate at present, it is necessary to promote the high-quality clinical therapeutic research. Based on the clinical guidelines, clinicians should carry out high-quality clinical research of NTM-PD treatment, focusing on the current urgent problems, especially the time of treatment initiation, optimization of treatment regimens, as well as prevention and rehabilitation strategies.